crossing96/oncoscreening huggingface dataset:
Comprehensive analyses of a tumor-infiltrating lymphocytes-related gene signature regarding the prognosis and immunologic features for immunotherapy in bladder cancer on the basis of WGCNA.	Tumor-infiltrating lymphocyte (TIL) is a class of cells with important immune functions and plays a crucial role in bladder cancer (BCa). Several studies have shown the clinical significance of TIL in predicting the prognosis and immunotherapy efficacy. TIL-related gene module was screened utilizing weighted gene coexpression network analysis. We screened eight TIL-related genes utilizing univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and multivariate Cox regression analysis. Then, we established a TIL-related signature model containing the eight selected genes and subsequently classified all patients into two groups, that is, the high-risk as well as low-risk groups. Gene mutation status, prognosis, immune cell infiltration, immune subtypes, TME, clinical features, and immunotherapy response were assessed among different risk subgroups. The results affirmed that the TIL-related signature model was a reliable predictor of overall survival (OS) for BCa and was determined as an independent risk factor for BCa patients in two cohorts. Moreover, the risk score was substantially linked to age, tumor staging, TNM stage, and pathological grade. And there were different mutational profiles, biological pathways, immune scores, stromal scores, and immune cell infiltration in the tumor microenvironment (TME) between the two risk groups. In particular, immune checkpoint genes' expression was remarkably different between the two risk groups, with patients belonging to the low-risk group responding better to immune checkpoint inhibition (ICI) therapy. In conclusion, our study demonstrates that the TIL-related model was a reliable signature in anticipating prognosis, immune status, and immunotherapy response, which can help in screening patients who respond to immunotherapy.	bladder
"""Seeing"" invisible volatile organic compound (VOC) marker of urinary bladder cancer: A development from bench to bedside prototype spectroscopic device."	"Urinary bladder cancer (UBC) is one of the most common cancers and has notoriously high risk of recurrence and mortality across the globe. Current clinical initial diagnostic approaches are either invasive or lacks sensitivity. In this study, an attempt has been made to invent a cost-effective, novel, portable diagnostic device based on the environmental sensitive fluorophores namely Nile Red (NR), Eosin Y (EY) and Rose Bengal (RB). They act as sensing agents for detecting volatile organic compounds (VOC) exclusively present in the urine sample of UBC patients and differentiate the UBC samples from the healthy control group. Upon exposure with a particular group of VOCs, a significant amount of increment in fluorescence intensities of NR, EY and RB were detected and recorded in our indigenously developed ""NABIL"" device. To check the performance of NABIL, the data collected from the device was compared with the conventional techniques by arranging a clinical trial with 21 healthy controls and 52 UBC patients. With the assistance of our analysis technique based on LabVIEW platform, very high sensitivity and accuracy from healthy controls have been achieved. For UBC patients, it shows impressive diagnostic results. In addition, depending on the sample processing mechanism, NABIL device can also reveal the grade of UBC and prognosis under treatment. Overall, this study contributes a novel, non-invasive, easy-to-use, inexpensive, real-time, accurate method for selectively UBC diagnosis, which can be useful for personalized care/diagnosis and postoperative surveillance, resulting in saving more lives."	bladder
Remarkable response to gemcitabine rechallenge in advanced urothelial carcinoma: a case report.	Therapeutic alternatives in advanced urothelial carcinoma are limited, especially in advanced lines, with only a few drugs having demonstrated relevant clinical benefit. This article discusses about a young patient with significant cardiovascular comorbidities, already treated with recommended first- and second-line drugs, and suffering from liver metastases. Despite the known poor prognosis of this disease and the few supporting data, given his peculiar clinical history, we opted to treat him with a third-line gemcitabine rechallenge with a notable response on his liver lesions. We present an intriguing case, both in terms of the therapeutic sequence and the disease course.	bladder
Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium).	PURPOSE: To investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: Patients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)-1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR - baseline eGFR; Δ2 = 6 months eGFR - POD-1 eGFR; Δ3 = 12 months eGFR - 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up. RESULTS: A total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up. CONCLUSION: Age, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.	bladder
Crosstalk of miRNAs with signaling networks in bladder cancer progression: Therapeutic, diagnostic and prognostic functions.	Urological cancers are considered as life-threatening diseases around the world. Bladder cancer is one of the most malignant urological tumors with high mortality and morbidity. Bladder cancer is a heterogenous disease and genetic alterations have shown to be key players in regulating its progression. Although conventional therapies are somewhat beneficial in improving prognosis and survival, bladder cancer patients suffer from recurrence. MicroRNAs (miRNAs) are endogenous short RNA molecules that do not encode proteins and show dysregulated expression in human cancers. miRNAs are regulators of vital biological processes in cells such as proliferation, migration, differentiation and apoptosis. Dysregulation of miRNAs is observed in bladder cancer and they are used as biomarkers for diagnosis and prognosis of patients. LncRNAs and circRNAs are modulators of bladder cancer progression via miRNA expression regulation. Overexpression of onco-suppressor miRNAs impairs bladder cancer progression, while oncogenic miRNAs drive tumor progression. Glycolysis and EMT mechanisms are two important factors for proliferation and migration of bladder cancer that are modulated by miRNAs. Furthermore, miRNAs can affect STAT3 and Wnt/β-catenin as instances of molecular factors in regulating bladder tumor progression. Bladder tumor response to drug therapy and radiotherapy is regulated by miRNAs. Hence, aim of current review is to provide function of miRNAs in bladder cancer based on their crosstalk with other molecular pathways and interaction with biological processes.	bladder
Flavokawain A is a natural inhibitor of PRMT5 in bladder cancer.	BACKGROUND: Protein arginine methyltransferases (PRMTs) regulate protein biological activity by modulating arginine methylation in cancer and are increasingly recognized as potential drug targets. Inhibitors targeting PRMTs are currently in the early phases of clinical trials and more candidate drugs are needed. Flavokawain A (FKA), extracted from kava plant, has been recognized as a potential chemotherapy drug in bladder cancer (BC), but its action mechanism remains unclear. METHODS: We first determined the role of a type II PRMT, PRMT5, in BC tissue samples and performed cytological experiments. We then utilized bioinformatics tools, including computational simulation, virtual screening, molecular docking, and energy analysis, to identify the potential use of PRMT5 inhibitors for BC treatment. In vitro and in vivo co-IP and mutation assays were performed to elucidate the molecular mechanism of PRMT5 inhibitor. Pharmacology experiments like bio-layer interferometry, CETSA, and pull-down assays were further used to provide direct evidence of the complex binding process. RESULTS: Among PRMTs, PRMT5 was identified as a therapeutic target for BC. PRMT5 expression in BC was correlated with poor prognosis and manipulating its expression could affect cancer cell growth. Through screening and extensive experimental validation, we recognized that a natural product, FKA, was a small new inhibitor molecule for PRMT5. We noticed that the product could inhibit the action of BC, in vitro and in vivo, by inhibiting PRMT5. We further demonstrated that FKA blocks the symmetric arginine dimethylation of histone H2A and H4 by binding to Y304 and F580 of PRMT5. CONCLUSIONS: In summary, our research strongly suggests that PRMT5 is a potential epigenetic therapeutic target in bladder cancer, and that FKA can be used as a targeted inhibitor of PRMT5 for the treatment of bladder cancer.	bladder
Accuracy of the European Association of Urology (EAU) NMIBC 2021 scoring model in predicting progression in a large cohort of HG T1 NMIBC patients treated with BCG.	BACKGROUND: Recently, the European Association of Urology Guidelines Panel updated the prognostic factor risk groups model for non-muscle-invasive bladder cancer (NMIBC) with the introduction of a new group of patients at very high risk (VHR). Furthermore, three additional clinical risk factors (i.e., age>70 years, multiple papillary tumors; tumor diameter >3 cm) were proposed. However, the new scoring model was created by analyzing data from patients who did not receive BCG intravesical therapy. METHODS: This is a retrospective multicenter study analyzing data of 920 patients with HGT1 NMIBC that underwent ReTUR e following BCG intravesical therapy. Patients were stratified into risk groups according to the 2021 new EAU NMIBC prognostic factor risk groups model. This study aimed to identify variables related to disease progression in a large cohort of HGT1 NMIBC patients who underwent both Re-TURB and BCG intravesical immunotherapy. RESULTS: Median follow-up was 51 months (IQR 41-75), according to EAU NMIBC 2021 scoring model 179 (19.5%) patients were at VHR. Progression-free survival at 5 years was 68.2% and 59.9% for the whole sample and the VHR group, respectively. At multivariable regression model size >3 cm, multifocal tumor, concomitant CIS and LVI were identified as independently associated with disease progression. CONCLUSIONS: Although patients at VHR are more likely to experience disease progression during follow-up, the European Association of Urology (EAU) NMIBC 2021 scoring model appears to be suboptimal in patients who underwent ReTUR and intravesical BCG therapy.	bladder
Ropivacaine inhibits proliferation and invasion and promotes apoptosis and autophagy in bladder cancer cells via inhibiting PI3K/AKT pathway.	Application of a certain concentration of local anesthetics during tumor resection inhibits the progression of tumor. The effects of ropivacaine in bladder cancer (BC) have never been explored. We explored the effects of ropivacaine on the progression of BC in vitro and in vivo. CCK8 assay and EDU staining was conducted to examine cell proliferation. Flow cytometry and transwell assay were performed to evaluate apoptosis and invasion, respectively. Expression of light chain 3 (LC3) was observed through immunofluorescence. Furthermore, the xenograft tumor model of BC was built to detect the effects of ropivacaine in vivo. IHC and TUNEL assay were conducted to detect cell proliferation and apoptosis in vivo. Ropivacaine inhibited the proliferation of T24 and 5639 cells with the 50% inhibitory concentration (IC50) of 20.08 and 31.86 µM, respectively. Ropivacaine suppressed the invasion ability and induces the apoptosis of cells. Besides, ropivacaine triggers obvious autophagy in BC cells. Moreover, ropivacaine blocks the PI3K/AKT signal pathway in BC cells. The impact of ropivacaine on cell viability, motility, and autophagy was reversed by 740 Y-P, the activator of PI3K/AKT signal pathway. The in vivo experiments demonstrated that ropivacaine inhibited the proliferation and mobility of BC. Ropivacaine has anti-carcinoma effects in BC via inactivating PI3K/AKT pathway, providing a new theoretical reference for the use of local anesthetics in the treatment of BC.	bladder
A transcriptional network of cell cycle dysregulation in noninvasive papillary urothelial carcinoma.	Human cancers display a restricted set of expression profiles, despite diverse mutational drivers. This has led to the hypothesis that select sets of transcription factors act on similar target genes as an integrated network, buffering a tumor's transcriptional state. Noninvasive papillary urothelial carcinoma (NIPUC) with higher cell cycle activity has higher risk of recurrence and progression. In this paper, we describe a transcriptional network of cell cycle dysregulation in NIPUC, which was delineated using the ARACNe algorithm applied to expression data from a new cohort (n = 81, RNA sequencing), and two previously published cohorts. The transcriptional network comprised 121 transcription factors, including the pluripotency factors SOX2 and SALL4, the sex hormone binding receptors ESR1 and PGR, and multiple homeobox factors. Of these 121 transcription factors, 65 and 56 were more active in tumors with greater and less cell cycle activity, respectively. When clustered by activity of these transcription factors, tumors divided into High Cell Cycle versus Low Cell Cycle groups. Tumors in the High Cell Cycle group demonstrated greater mutational burden and copy number instability. A putative mutational driver of cell cycle dysregulation, such as homozygous loss of CDKN2A, was found in only 50% of High Cell Cycle NIPUC, suggesting a prominent role of transcription factor activity in driving cell cycle dysregulation. Activity of the 121 transcription factors strongly associated with expression of EZH2 and other members of the PRC2 complex, suggesting regulation by this complex influences expression of the transcription factors in this network. Activity of transcription factors in this network also associated with signatures of pluripotency and epithelial-to-mesenchymal transition (EMT), suggesting they play a role in driving evolution to invasive carcinoma. Consistent with this, these transcription factors differed in activity between NIPUC and invasive urothelial carcinoma.	bladder
CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients.	High grade non-muscle-invasive bladder tumours are treated with transurethral resection followed by recurrent intravesical instillations of Bacillus Calmette Guérin (BCG). Although most bladder cancer patients respond well to BCG, there is no clinical parameter predictive of treatment response, and when treatment fails, the prognosis is very poor. Further, a high percentage of NMIBC patients treated with BCG suffer unwanted effects that force them to stop treatment. Thus, early identification of patients in which BCG treatment will fail is really important. Here, to identify early stage non-invasive biomarkers of non-responder patients and patients at risk of abandoning the treatment, we longitudinally analysed the phenotype of cells released into the urine of bladder cancer patients 3-7 days after BCG instillations. Mass cytometry (CyTOF) analyses revealed a large proportion of granulocytes and monocytes, mostly expressing activation markers. A novel population of CD15(+)CD66b(+)CD14(+)CD16(+) cells was highly abundant in several samples; expression of these markers was confirmed using flow cytometry and qPCR. A stronger inflammatory response was associated with increased cell numbers in the urine; this was not due to hematuria because the cell proportions were distinct from those in the blood. This pilot study represents the first CyTOF analysis of cells recruited to urine during BCG treatment, allowing identification of informative markers associated with treatment response for sub-selection of markers to confirm using conventional techniques. Further studies should jointly evaluate cells and soluble factors in urine in larger cohorts of patients to characterise the arms of the immune response activated in responders and to identify patients at risk of complications from BCG treatment.	bladder
Assessment of cause-specific mortality and disability-adjusted life years (DALYs) induced by exposure to inorganic arsenic through drinking water and foodstuffs in Iran.	The health risk and burden of disease induced by exposure to inorganic arsenic (iAs) through drinking water and foodstuffs in Iran were assessed. The iAs levels in drinking water and foodstuffs (15 food groups) in the country were determined through systematic review of three international databases (PubMed, Scopus, and Web of Science) and meta-analysis. Based on the results of the systematic review and meta-analysis, the average iAs levels in drinking water and all the food groups at the national level were lower than the maximum permissible levels. The total average non-carcinogenic risk of dietary exposure to iAs in terms of hazard index (HI) was 3.4. The average incremental lifetime cancer risk (ILCR) values of dietary exposure to iAs were determined to be 1.5 × 10(-3) for skin cancer, 1.0 × 10(-3) for lung cancer, and 4.0 × 10(-4) for bladder cancer. Over two-thirds of the non-carcinogenic and carcinogenic risk of dietary exposure to iAs was attributed to bread and cereals, drinking water, and rice. The total annual cancer incidence, deaths, disability-adjusted life years (DALYs), death rate, and DALY rate (per 100,000 people) were assessed to be 3347 (95 % uncertainty interval: 1791 to 5999), 1302 (697 to 2336), 72,606 (38,833 to 130,228), 1.6 (0.87 to 2.9), and 91 (49 to 160). The contribution of mortality in the attributable burden of disease was 95.1 %. The contributions of the causes in the attributable burden of disease were 72 % for lung cancer, 16 % for bladder cancer, and 12 % for skin cancer. Due to the significant attributable burden of disease, national and subnational action plans consisting of multi-disciplinary approaches for risk management of dietary exposure to iAs, especially for the higher arsenic-affected areas and high-risk population groups in the country are recommended.	bladder
A Multilayer Nanofibrous Mat for the Topical Chemotherapy of the Positive Margin in Bladder Cancer.	Treatment of positive margins after solid tumor resection remains a significant challenge for clinicians. Owing to unique structural features, electrospun nanofibrous mats are promised to be an implantable antitumor system through the delivery of active agents in a controlled manner. In this study, we utilized sequential electrospinning to fabricate a multilayer mat in which gemcitabine (GEM) and cisplatin (CDDP) were electrospun individually in distinct layers. By designing the structure, the multilayer mat could deliver antitumor agents sustainedly and prolong the release of GEM, which is loaded in the inner layer. In vitro assays show that the multilayer mats effectively inhibit bladder cancer (BC) cells and elevate apoptosis. In animal models of BC, the implantable drug-loaded fibrous mat can effectively treat positive margins and prevent local recurrence. Moreover, the local delivery of GEM and CDDP significantly lowers liver toxicity compared with systemic chemotherapy. In summary, a multilayer nanofibrous mat is developed for the localized and controlled delivery of GEM, dramatically improving the treatment of residual tumors and preventing BC recurrence. Impact statement The designed multilayer nanofibrous mats can achieve two chemotherapeutic drugs (gemcitabine and cisplatin) co-loading and time-programmed sustained release, significantly improving our previous study. The antitumor effect of the drug-loaded mat in vivo and in vitro was sufficiently demonstrated. We expect to bring a new strategy of topical chemotherapy for treating positive surgical margins in bladder cancer.	bladder
A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer.	BACKGROUND: Recurrence of non–muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection. METHODS: In this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)–guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat. RESULTS: A total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months’ median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444). CONCLUSIONS: PDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)	bladder